Moxiclav

Amoxicillin trihydrate, potassium clavulanate.

MOXICLAV 1g: Each tablet contains 875mg Amoxicillin as the trihydrate and 125mg Clavulanic Acid as the Potassium salt.
MOXICLAV 625mg: Each tablet contains 500mg Amoxicillin as the trihydrate and 125mg Clavulanic Acid as the Potassium salt.
MOXICLAV 375mg: Each tablet contains 250mg Amoxicillin as the trihydrate and 125mg Clavulanic Acid as the Potassium salt.
MOXICLAV Dry Powder for Oral Suspension 156.25mg/5 ml: when reconstituted each teaspoonful (5ml) contains amoxicillin trihydrate equivalent to 125mg amoxicillin base and clavulanate potassium equivalent to 31.25mg Clavulanic acid.
MOXICLAV Forte Dry Powder for Oral Suspension 312.5mg/5ml: when reconstituted, each teaspoonful (5ml) contains amoxicillin trihydrate equivalent to 250mg amoxicillin base and clavulanate potassium equivalent to 62.5mg Clavulanic acid.

MOXICLAV is a combination of amoxicillin, broad spectrum penicillin and potassium clavulanate, a progressive and irreversible inhibitor of beta-lactamase enzymes. The presence of potassium clavulanate protects Amoxicillin from destruction and subsequent loss of bacterial activity by the beta-lactamase enzymes produced by many Gram-negative and Gram-positive bacteria.
MOXICLAV will not only eliminate primary pathogens but also will not be inactive by non pathogenic beta-lactamase producing organisms at the site of infection.
Pharmacology: Pharmacodynamics: Moxiclav is a combination of amoxicillin (as amoxicillin trihydrate) and clavulanic acid (as potassium clavulanate). Amoxicillin is semisynthetic penicillin with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. It acts by inhibiting the biosynthesis of cell wall mucopeptide. However, Amoxicillin is susceptible to degradation from β-lactamases, and therefore its spectrum of activity does not include β-lactamase producing microorganisms.
Clavulanic acid is a β-lactam antibiotic, structurally related to the penicillins, which posses the ability to inactivate a wide range of β-lactamase enzymes, commonly found in microorganisms resistant to penicillins and cephalosporins.
The combination of amoxicillin and clavulanic acid results in the protection of amoxicillin from degradation by β-lactamase enzymes, and effectively extends the antibiotic spectrum; of amoxicillin; to include many bacteria, normally resistant to amoxicillin and other β-lactam antibiotics.
Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in MOXICLAV anticipates this defense& mechanism by blocking the β-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin's rapid bactericidal effect at concentrations readily attainable in the body.
Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as MOXICLAV, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
MOXICLAV is bactericidal to a wide range of organisms including: Gram-positive: Aerobes: Enterococcus faecalis*, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus*, Coagulase negative staphylococci* (including Staphylococcus epidermidis*), Corynebacterium species, Bacillus anthracis*, Listeria monocytogenes.
Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.
Gram-negative: Aerobes: Haemophilus influenzae*, Moraxella catarrhalis*, Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella species* Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitidis*, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides species* including B. fragilis.
*including Beta-lactamase producing strains resistant to ampicillin and amoxicillin.
Pharmacokinetics: The pharmacokinetics of the two components of MOXICLAV is closely matched. Peak serum levels of both occur about one hour after oral administration. Absorption of MOXICLAV is optimized at the start of a meal. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Doubling the dosage of MOXICLAV approximately doubles the serum levels achieved.
Toxicology: Preclinical safety data: No further information of relevance.
Microbiology: Bacteriology: MOXICLAV is bactericidal to a wide range of Gram-negative and Gram-positive bacteria including many clinically important beta-lactamase producing resistant organisms including: GRAM-POSITIVE: Aerobes: Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, Streptococcus viridans, Streptococcus pyogenes, Streptococcus faecalis, Bacillus anthracis, Listeria monocytogenes and Corynebacterium species.
Anaerobes: Clostridium species, Peptostreptococcus species, Peptococcus species.
GRAM-NEGATIVE: Aerobes: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species, Salmonella species, Shigella species, Bordetella pertussis, Yersinia enterocolitica, Gardnerella Vaginalis, Brucella species, Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Pasteurella multocida and Vibrio cholerae.
Anaerobes: Bacteroides species, including Bacteroides fragilis.
Including beta-lactamase producing strains resistant to ampicillin and amoxicillin.

MOXICLAV is indicated for the treatment of bacterial infections such as: Upper Respiratory Tract Infections (including ENT): tonsillitis, sinusitis, otitis media.
Lower Respiratory Tract Infections: acute exacerbations of chronic bronchitis, lobar and bronchopneumonia.
Genito-urinary tract infections: cystitis, urethritis, pyelonephritis; Skin and soft tissue infections, e.g. boils, abscesses, cellulitis , wound infections.
Bone and joint infections e.g. osteomyelitis.
Other infections e.g. septic abortion, puerperal sepsis, intra­-abdominal sepsis; A comprehensive list of susceptible organisms is previously provided in Pharmacology: Pharmacokinetics under Actions.

Adults and children over 14 years: Mild - Moderate infections: MOXICLAV 375 mg tablet three times a day or one MOXICLAV 625 mg tablet two times a day.
Severe infections: MOXICLAV 625 mg tablet three times a day or one MOXICLAV 1 g tablet twice daily.
Children: Children 7-14 years: 10 ml MOXICLAV suspension three times a day or 5 ml MOXICLAV Forte suspension three times a day.
Children 2-7 years: 5 ml MOXICLAV suspension three times a day.
Children 9 months-2 years: 2.5 ml of MOXICLAV oral suspension (125 mg/5 ml) every 8 hours. In children less than 2 years old the daily administered dose of clavulanic acid should not be greater than 5 mg/kg of body weight. In case of severe infections dosage should not be increased.
Treatment with MOXICLAV should not be extended beyond 14 days unless otherwise advised by physician.
Dosage in Renal Impairment: Adults: Mild impairment (Creatinine clearance >30 ml/min): No changes in dosage.
Moderate impairment (Creatinine clearance 10-30 ml/min): one 375 mg tablet or one 625 mg tablet 12 hourly. Severe impairment (Creatinine clearance < 10ml/min): not more than one 375 mg tablet every 12 hours.
Children: For children with a Creatinine clearance >30 ml/min no adjustment in dosage in required.
For children with Creatinine clearance <30ml/min MOXICLAV Dry Powder for oral suspension and MOXICLAV Forte Dry Powder for oral suspension are not recommended.
Dosage in hepatic impairment: Dose with caution; monitor hepatic function at regular intervals.
Preparation and administration: Tablets should be swallowed whole without chewing. If required, tablets may be broken in half and swallowed without chewing.
To minimize potential gastrointestinal intolerance, administer at the start of a meal. The absorption of MOXICLAV is optimized when taken at start of a meal.

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically to the water electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Precautions).
MOXICLAV can be removed from the circulation by haemodialysis.

MOXICLAV is contraindicated in patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.
MOXICLAV is contraindicated in patients with a previous history of MOXICLAV associated jaundice/hepatic dysfunction.

Before initiating therapy with MOXICLAV careful enquiry should be made concerning hypersensitivity reactions to penicillins and cephalosporins or other allergens.
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity (see Contraindications). If an allergic reaction occurs, MOXICLAV therapy must be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous (i.v.) steroids and airway management (including intubation) may also be required.
MOXICLAV should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Prolongation of bleeding time and prothrombin time has been reported in some patients receiving MOXICLAV. MOXICLAV should be used with care in patients on anti-coagulation therapy.
Changes in liver function tests have been observed in some patients receiving MOXICLAV. The clinical significance of these changes is uncertain. MOXICLAV should be used with caution in patients with evidence of hepatic dysfunction.
Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased.
In patients with renal impairment MOXICLAV dosage should be adjusted as recommended. (See Dosage & Administration.)
In patients with reduced urine output, crystalluria has been observed very rarely , predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Overdosage).
Effects on Ability to Drive and Use Machines: Adverse effects on the ability to drive or operate machinery have not been observed.

Reproduction studies in animals (mice and rats) with orally and parenterally administered Moxiclav have shown no teratogenic effects. In a single study in women with pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Moxiclav may be associated with an increased risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.
Moxiclav may be administered during the period of lactation.
With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.

Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at < 1/10,000.) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency: very common: ≥1/10; common: ≥1 /100 and <1/10; uncommon: ≥1/1000 and <1/100; rare ≥1/10,000 and <1/1000; very rare <1/10,000.
Infections and infestations: Common: mucocutaneous candidiasis.
Blood and lymphatic system disorders: Rare: reversible leucopenia (including neutropenia) and thrombocytopenia.
Very rare: reversible agranulocytosis and haemolytic anaemia, prolongation of bleeding time and prothrombin time (see Precautions).
Immune system disorders: Very rare: angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis.
Nervous system disorders: Uncommon: dizziness , headache.
Very rare: aseptic meningitis, reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal disorders: Adults: Very common: diarrhoea.
Common: nausea, vomiting.
Children: Common: diarrhoea, nausea, vomiting.
All populations: Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking MOXICLAV the start of a meal.
Uncommon: indigestion.
Very rare: antibiotic-associated colitis (including pseudo membranous colitis and hemorrhagic colitis); black hairy tongue.
Hepatobillary disorders: Uncommon: a moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.
Very rare: hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects.
Skin and subcutaneous tissue disorders: Uncommon: skin rash, pruritus, urticaria.
Rare: erythema multiforme.
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalized exanthemous pustulosis (AGEP) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Renal and urinary disorders: Very rare; interstitial nephritis, crystalluria (see Overdosage).

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with Moxiclav may result in increased and prolonged blood levels of amoxicillin but not of clavulanate.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Moxiclav and allopurinol.
In common with other antibiotics, Moxiclav may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Concurrent administration of amoxicillin with tetracycline antibiotics decreases the bactericidal action of amoxicillin.
Drug Laboratory Interactions: False-positive results may be obtained when testing for the presence of glucose in urine, using a copper-sulfate reagent.

MOXICLAV preparations should be store in a dry place protected from light at temperature not exceeding 25°C.
Once reconstituted MOXICLAV suspension must be stored in a refrigerator and used within 7 days. If dilution of the suspension is required water should be used.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

POM